Innate immune responses Flashcards

1
Q

What are the two main features of the innate immune response?

A

Non-specific

Rapid - initial response takes a few hours

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2
Q

What are the molecules involved in the innate immune response?

A

Antimicrobial peptides

Complement

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3
Q

What are the cells involved in the innate immune response?

A

Phagocytes

Natural Killer Cells

Interferons

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4
Q

What are the four host defences?

A

Anatomical and chemical barriers

Intrinsic

Innate immunity

Acquired immunity

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5
Q

What are the anatomical and chemical barriers preventing pathogens from causing disease?

A

Skin

Mucus

Tears

Preformed soluble molecules

Low pH

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6
Q

Which cells take part in intrinsic immunity?

A

Always present in all uninfected cells

They have the ability to prevent viruses from getting into the cell

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7
Q

Which processes form part of the intrinsic immunity?

A

Autophagy

RNA silencing

Antiviral proteins

Apoptosis

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8
Q

Examples of cellular proteins that inhibit viral replication

A

TRIM

APOBEC3

Tetherin

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9
Q

Examples of soluble mechanisms of innate immunity

A

Antimicrobial enzymes

Antimicrobial proteins

Complement

Cytokines

Acute phase proteins

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10
Q

Examples of antimicrobial proteins

A

Defensins

Cathelicidins

Histatins

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11
Q

How do defensins provide immunity?

A

Small cationic antimicrobial peptides that enter the negatively charged membrane

Form pores

Leads to a loss of small-molecule gradients

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12
Q

What are the two main structural families of defensins?

A

Alpha defensins

Beta defensins

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13
Q

Which family of defensins is constitutively expressed?

A

Alpha defensins

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14
Q

What are the two cellular responses in innate immunity in responser to danger inputs?

A

Response to threat

Communication to other immune cells

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15
Q

What are the three types of PRRs?

A

Intracellular

Cell surface

Secreted

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16
Q

Examples of DAMPs

A

Ion concentration changes

DNA

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17
Q

What type of antigens are recognised by the innate immune system?

A

Structures shared by classes of microbes

100 receptors = 100 molecules recognised

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18
Q

How many types of receptors recognise antigens that activate the innate immune system?

A

Around 100

Germline encoded

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19
Q

What type of antigens are recognised by the adaptive immunity?

A

Specific epitoptes

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20
Q

How many molecules can be recognised by the adaptive immune system?

A

> 10^7

Receptor genes undergo somatic recombination, leading to a huge diversity in the molecules recognised

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21
Q

What are the two classes of receptors making up the adaptive immune system?

A

Antibody

TCR

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22
Q

What is the main difference of the recognition potential of the adaptive immunity vs the innate immunity?

A

The adaptive immune receptors undergo somatic recombination

So although there are two main types of receptors (BCR and TCR), there is high variability in their subtypes

The innate immune receptors do not undergo somatic recombination, and the receptors they produce are used to recognise the different antigens

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23
Q

What are the two main types of PRRs?

A

Soluble molecules

Cell associated molecules

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24
Q

Examples of soluble PRRs

A

Pentraxins

Ficolins

Collectins

Complement proteins

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25
Q

Examples of cell associted PRRs

A

C-type lectins

TLR

Scavenger receptors

NOD like receptors

RIG-like receptors

c-GAS

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26
Q

What is the difference between different cell associated PRRs?

A

Found in different locations on the cell

Cell surface = C-type lectins, TLR

Inside endosomes = TLR

Cytosolic = NOD like receptors, RIG-like receptors

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27
Q

How are soluble PRRs useful?

A

Recognise presence of a pathogen in the circulation

28
Q

Describe the specificity of PRRs

A

Different PRRs recognise different patterns

Elicit specific responses upon binding to a pattern

29
Q

Describe TLR signalling

A
  1. Ligand engages TLR
  2. Association of protein kinases to adaptor proteins
  3. Activation of transcription factors
  4. Formation of respiratory bursts, cytokines, chmokines, MMPs, antimicrobial peptides
30
Q

What is the function of IRF?

A

Interferon regulatory factor

Generally antiviral

31
Q

What is the function of NFkB?

A

Generally inflammatory

32
Q

What are the 3 major classes of cytosol PRRs?

A

NOD like receptors

RIG like receptors

Cytosolic DNA sensors

33
Q

What do NOD like receptors recognise?

A

NOD1/2 recognise the bacterial cell wall

34
Q

What do RIG like receptors recognise?

A

Viral RNA

35
Q

What do cytosolic DNA sensors recognise?

A

Microbial DNA in the cytoplasm

36
Q

What are the cells of the innate immunity?

A

Macrophages

Dendritic cells

Neutrophils

Eosinophils

Basophils

Mast cells

Natural killer cells

37
Q

What is special about neutrophils, eosinophils and basophils?

A

They are polymorphonuclear leukocytes

Contain granules that stain in different ways to allow for identification

38
Q

What happens to macrophages and DCs once stimulated by PRRs?

A

Increase their antigen presenting capacity

Lead to the development of the adaptive immunity

39
Q

Describe the process by which phagocytosis destroys pathogens

A
  1. Chemotaxis
  2. Adherence via PAMP recognition
  3. Cell activation via PRR
  4. Initiation of phagocytosis
  5. Phagosome formation
  6. Phagolysosome formation
  7. Bacterial killing and digestion
  8. Release of degradation products
40
Q

What is the main purpose of opsonisation?

A

Allows the process of phagocytosis to function more efficiently

41
Q

How do cells carrying out phagocytosis recognise the microbe?

A

The microbe is bound to antibodies

The FcR of the phagocytosing cell recognises the Fc portion of the antibody

42
Q

What three main processes lead to bacterial killing in the phagolysosome?

A

Enzymes

Reactive oxygen species

Reactive nitrogen species

43
Q

Examples of ROS

A

Hydroxyl radical

Superoxide

44
Q

Oxygen-independent mechanisms of pathogen destruction

A

Damage to microbial membrane by

  • cathepsin G
  • defensins
  • cationic proteins
  • bacteriidial permeability increasing proteins

Splitting of mucopeptide in the bacterial cell wall by lyzosymes

Complex with iron through lactoferrin

Digestion of killed organisms through proteolytic and hydrolytic enzymes

45
Q

What is phagocytosis?

A

Ingestion and killing of extracellular microbes

46
Q

Which cells carry out phagocytosis?

A

Neutrophils

Monocytes

Macrophages

47
Q

From which cells are macrophages derived from?

A

Monocytes

48
Q

Which are the first cells to respond to infection?

A

Neutrophils

49
Q

What type of cell are natural killer cells?

A

Large granular lymphocytes

50
Q

Where are natural killer cells found?

A

In the circulation

51
Q

What percentage of circulating leykocytes do NK cells make up?

A

5-20%

52
Q

NK cells destroy bacteria

TRUE or FALSE

A

FALSE

Recognise changes in self cells

53
Q

What do NK cells respond to?

A

Cells with missing self antigens

Stressed cells

Viral haemagglutinins

Antibody-coated cells

54
Q

What are the two responses evoked by NK cells?

A

Cytotoxicity

IFNy release

55
Q

What are NK cells an important source of?

A

Interferon gamma

56
Q

Describe what is meant by ‘NK cells react to cells with abnormal self receptors’

A

Cells express activator proteins as well as MHC I

MHC I binds to the inhibitory receptors on NK cells, preventing them from causing cell death

In cancer or infected cells, they can overexpress activatory proteins or reduce expression of MHC I

This is detected by NK cells, which cause death of these abnormal cells

57
Q

What are the mechanisms of NK cell killing?

A

Granzymes enter target cell via perforin pore or endocytosis

Activation of apoptotic pathways

58
Q

Which cell links the adaptive and innate immune responses?

A

Dendritic cells

59
Q

Which scientist first described Dendritic cells?

A

Langerhans

60
Q

What are the two states dendritic cells are found in?

A

Immature

Mature

61
Q

Compare the MHC expression between mature and immature DCs

A

Mature DCs express MHC highly

Immature has low surface MHC

62
Q

Do mature or immature DCs have high phagocytic activity?

A

Immature DCs are highly phagocytic

63
Q

How do DCs become mature?

A

Through detection of microbial products

Inflammatory cytokines

Damaged host cells

64
Q

Give a brief overview of the role of DCs in the innate immune response

A

Immature DCs are found in many tissues

Mature in inflamed tissues following cytokine signals and antigen capture

Mature DCs migrate to lymph nodes and present antigenic peptides to T cells

65
Q

What type of cells are dendritic cells?

A

Professional antigen presenting cells

Activate naive T cells

66
Q

How do NK cells carry out cell death the activation of apoptotic pathways?

A

FASL on NK cells binds to Fas on target cell

FADD becomes activated upon binding, which turns procaspase-8 into caspase-8

Caspase-8 activates Caspase-3

Caspase-3 leads to apoptosis

67
Q

What is the marker for mature dendritic cells?

A

CCR7

Immature DCs are also CCR7+, but also express CCR2,5,6